New 21-nordammarane saponins with anti-inflammatory and cytotoxic activities from Lavigeria macrocarpa Oliv.

Chemical investigation of the ethanol extract from the stems and roots of the medicinal plant Lavigeria macrocarpa led to the isolation and structure elucidation of three previously unreported 21-nordammarane-type saponins namely 6α,27-dihydroxy-3,20-dioxo-21-nordammar-24-(Z)-ene 27-O-[α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranoside] (1), 6α,27-dihydroxy-3-oxo-21-nordammar-24-(Z)-ene 27-O-ß-D-glucopyranoside (2), and 2α,3ß,6α,27-tetrahydroxy-21-nordammar-24-(Z)-ene 27-O-ß-D-glucopyranoside (3) trivially named lavigemacrocarposide A-C, along with eight known secondary metabolites. Acid hydrolysis of lavigemacrocarposide A yielded a new prosapogenin namely 6α,27-dihydroxy-3,20-dioxo-21-nordammar-24-(Z)-ene 27-O-ß-D-glucopyranoside (1a) and the previously unreported artefactual aglycones 1b and 1c. Their structures were elucidated by spectroscopic analyses including mass spectrometry, 1D and 2D NMR as well as chemical evidence. The EtOH extract, some isolated compounds as well as the prosapogenin (1a) and compounds 1b and 1c were evaluated for anti-inflammatory and cytotoxic activity. Icacine (5) exhibited a significant cytotoxicity against both HeLa and MCF-7 cell lines with an IC50 value of 0.78 µg/mL. All the tested compounds showed more that 50% inhibition of NO production, except for 1 and 2.

Cytotoxicity, antioxidant and antibacterial activity of four compounds produced by an endophytic fungus Epicoccum nigrum associated with Entada abyssinica

ABSTRACT Four compounds including beauvericin, parahydroxybenzaldehyde, indole-3-carboxylic acid and quinizarin were isolated from endophytic fungus Epicoccum nigrum and their cytotoxicity, antibacterial and antioxidant activity were evaluated. Beauvericin had remarkable activity against two Gram-negative strains (Bacillus cereus and Salmonella typhimurium) with respective MIC values of 3.12 and 6.25 µg/ml. All the compounds had weak cytotoxic effect on both normal and tumor cells. LC50 values ranged from 40.42 to 86.56 µg/ml, 31.87 to 86.57 µg/ml and 21.59 to 67.27 µg/ml on Vero cells, THP-1 and RAW 264.7 respectively. The present study showed that these compounds could be developed for the formulation of antioxidant-rich therapeutic diets and as a therapeutic agent against bacterial infections.

Cytotoxicity, nitric oxide and acetylcholinesterase inhibitory activity of three limonoids isolated from Trichilia welwitschii (Meliaceae).

BACKGROUND: Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the plant kingdom is mainly confined to plant families of Meliaceae and Rutaceae. Owing to their wide range of pharmacological and therapeutic properties, this study was aimed at investigating the potential nitric oxide (NO) and acetylcholinesterase (AChE) inhibitory activity and the cytotoxicity of three limonoids: trichilia lactone D5 (1), rohituka 3 (2) and dregeanin DM4 (3), isolated from Trichilia welwitschii C.DC. RESULTS: Results indicated that the three limonoids had low cytotoxicity towards Vero cells with LC50 values ranging from 89.17 to 75.82 µg/mL. Compounds (2) and (3) had lower cytotoxicity compared to puromycin and doxorubicin used as reference cytotoxic compounds. Compound (1) (LC50 of 23.55 µg/mL) had good antiproliferative activity against RAW 264.7 cancer cells. At the lowest concentration tested (0.5 µg/mL), compound (2) and (3) released the lowest amount of nitric oxide (2.97 and 2.93 µM, respectively). The three limonoids had anti-AChE activity with IC50 values ranged of 19.13 µg/mL for (1), 34.15 µg/mL for (2) and 45.66 µg/mL for (3), compared to galantamine (IC50 of 8.22 µg/mL) used as positive control. CONCLUSION: The limonoid compounds studied in this work inhibited nitric oxide production in LPS-stimulated macrophages and had anti-AChE activity. Trichilia lactone D5 had potential antiproliferative activity against RAW 264.7 cancer cells. The limonoids had low cytotoxicity towards Vero cells lines. This study provided further examples of the importance of limonoids compounds as potential AChE inhibitors and anti-inflammatory agents targeting the inhibition of NO production.

The anti-inflammatory and antioxidant activity of 25 plant species used traditionally to treat pain in southern African.

BACKGROUND: Inflammation is a common risk factor in the pathogenesis of conditions such as infections, arthritis, type 2 diabetes mellitus, obesity and cancer. An ethnobotanical survey of medicinal plants used traditionally to treat inflammation and related disorders such as pain, arthritis and stomach aches in southern Africa led to the selection of 25 plant species used in this study. METHODS: The antioxidant activities of acetone extracts were determined by measuring the free radical scavenging activity and ferric reducing ability, respectively. The anti-inflammatory activities of the extracts were determined by measuring the inhibitory effect of the extracts on the activities of the pro-inflammatory enzyme, lipoxygenase and inducible nitric oxide synthase. RESULTS: Extracts of Peltophorum africanum had good antioxidant activity with IC50 values of 4.67 ± 0.31 µg/mL and 7.71 ± 0.36 µg/mL compared to that of the positive control ascorbic acid (2.92 ± 0.14 µg/mL and 13.57 ± 0.44 µg/mL), using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and 2,2'-azinobis (3-ethylbenzthiazoline-6-sulphonic acid (ABTS) methods, respectively. The metabolism of linoleic acid to leukotriene derivatives by 15-lipoxygenase (15-LOX) was also inhibited by the crude acetone extracts of Peltophorum africanum (IC50 = 12.42 µg/mL), Zanthoxylum capense (IC50 = 14.92 µg/mL) compared to the positive control quercetin (IC50 = 8.75 µg/mL). There was a poor correlation between the flavonoid content and 15-LOX inhibition by the extracts (R(2) = 0.05), indicating that flavonoids are not involved in LOX inhibition. Extracts of Clausena anisata, at a concentration of 6.25 µg/mL inhibited nitric oxide production by RAW 264.7 macrophage cell lines in vitro by 96 %. The extracts of Zanthoxylum capense were the least cytotoxic (IC50 > 1000 µg/mL) when the extract toxicity was determined against Vero (African green Monkey) kidney cell lines. CONCLUSION: Some plant species used traditionally to treat pain have reasonable anti-inflammatory activity and flavonoids are probably not involved in this process.

Cytotoxicity, nitric oxide and acetylcholinesterase inhibitory activity of three limonoids isolated from Trichilia welwitschii (Meliaceae)

BACKGROUND: Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the plant kingdom is mainly confined to plant families of Meliaceae and Rutaceae. Owing to their wide range of pharmacological and therapeutic properties, this study was aimed at investigating the potential nitric oxide (NO) and acetylcholinesterase (AChE) inhibitory activity and the cytotoxicity of three limonoids: trichilia lactone D5 (1), rohituka 3 (2) and dregeanin DM4 (3), isolated from Trichilia welwitschii C.DC. RESULTS: Results indicated that the three limonoids had low cytotoxicity towards Vero cells with LC50 values ranging from 89.17 to 75.82 µg/mL. Compounds (2) and (3) had lower cytotoxicity compared to puromycin and doxorubicin used as reference cytotoxic compounds. Compound (1) (LC50 of 23.55 µg/mL) had good antiproliferative activity against RAW 264.7 cancer cells. At the lowest concentration tested (0.5 µg/mL), compound (2) and (3) released the lowest amount of nitric oxide (2.97 and 2.93 µM, respectively). The three limonoids had anti-AChE activity with IC50 values ranged of 19.13 µg/mL for (1), 34.15 µg/mL for (2) and 45.66 µg/mL for (3), compared to galantamine (IC50 of 8.22 µg/mL) used as positive control. CONCLUSION: The limonoid compounds studied in this work inhibited nitric oxide production in LPS-stimulated macrophages and had anti-AChE activity. Trichilia lactone D5 had potential antiproliferative activity against RAW 264.7 cancer cells. The limonoids had low cytotoxicity towards Vero cells lines. This study provided further examples of the importance of limonoids compounds as potential AChE inhibitors and anti-inflammatory agents targeting the inhibition of NO production.

Cytotoxicity and antimicrobial activity of the methanol extract and compounds from Polygonum limbatum.

The present study was designed to investigate the antimicrobial activity and the cytotoxicity of the methanol extract (PLA) as well as fractions (PLA1-4) and compounds [cardamomin (1), (±)-polygohomoisoflavanone (2), (S)-(-)-pinostrobin (3), 2',4'-dihydroxy-3',6'-dimethoxychalcone (4), (2S)-(-)-5-hydroxy-6,7-dimethoxyflavanone (5), and (2S)-(-)-5,7-dimethoxyflavanone (6)] obtained from leaves of Polygonum limbatum. The microbroth dilution was used to determine the minimal inhibitory concentration (MIC) of the samples against 11 microbial strains including Candida albicans, C. krusei, C. tropicalis, Aspergillus fumigatus, Pseudomonas aeruginosa, Escherichia coli, vancomycin-resistant Enterococcus faecalis (VRE), Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S.epidermidis, and Mycobacterium tuberculosis H37Rv. The sulphorhodamine B cell growth inhibition assay was used to assess the cytotoxicity of the above samples on lung A549 adenocarcinoma, breast carcinoma MCF-7, prostate carcinoma PC-3, cervical carcinoma HeLa, and the acute monocytic leukemia cell line THP-1. The results of the MIC determination indicated that, apart from fraction PLA3, all other fractions as well as PLA and compound 3 were selectively active. MIC values were noted on 100 % of the 11 tested microorganisms for fraction PLA3, 72.7 % for PLA, fraction PLA2, and compound 4, 63.6 % for PLA1, and 54.5 % for fraction PLA4. The results of the cytotoxicity assay revealed that, except for A459 cells, more than 50 % inhibition of the proliferation was obtained with each of the tested samples on at least one of the four other cell lines. IC50 values below 4 µg/mL were obtained with 1 and 4 on THP-1 cells. The overall results of the present study provided baseline information for the possible use of Polygonum limbatum as well as some of the isolated compounds for the control of cancer diseases and mostly leukemia.